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BACKGROUND:Contraction of three-dimensional collagen gels has been used as a model for the contraction which characterizes both normal wound healing and the development of fibrosis in the tissue. Several factors and cytokines,such as tumor necrosis factor alpha (TNF-α), interleukin-1, prostaglandin E2 and insulin have been proved to play important roles in collagen remodeling in vitro as well as serum extravasation during the fibrotic progress.OBJECTIVE: To observe extracellular collagen matrix contraction and apoptosis of fetal lung fibroblasts in TNF-α,interleukin-1, insulin, prostaglandin E2, albumin and globum under three-dimensional culture, and investigate the effects of cytokines, insuin, serum and serum protein on the remodeling and fibrotic formation of lung tissue.DESIGN: A randomized controlled experiment.SETTING: Department of Respiratory Medicine, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA.MATERIALS: The experiment was carried out The experiments were carried out in the respiratory laboratory of Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from August 2005 to January 2006. Human fetal lung fibroblasts (American Type Culture Collection), Dulbecco's modified Eagle's medium (DMEM) and fetal bovine serum, insulin, transforming growth factor (TGF) (R&D), prostaglandin E2, type Ⅰ collagen was extracted from rat-tail tendons.METHODS: In order to investigate the effect of initial collagen concentration in the gels on the contractility of fibroblasts,the appropriate amount of collagen was mixed with distilled water, four fold-concentrated DMEM, and cells were suspended so that the mass concentration was 0.75-2.0 g/L, with a physiological ionic strength and the desired cell concentration. In order to investigate the effect of cell number in the gels on the contraction, the cellular concentration fibroblasts in the gels were prepared to 0.2×107-4×107 L-1. The areas of floating gels were measured daily and the contraction was calculated by contrasting the initial size (％ of initial area). Different serum concentrations (0.01％-0.5％)in the medium were prepared, the serum albumin (0.1％) or globulin (0.1％) were added to the serum-free culture medium to observe the gel contraction. TGF (10 mg/L), interleukin-1 (10 mg/L), insulin (1 mg/L) and prostaglandin E2 (0.1 μmol/L) were added to observe the effects of cytokines and insulin on fibroblasts-mediated collagen gel contraction.The DNA content and cellular survivability in gels in collagen were determined.MAIN OUTCOME MEASURES: Effect of lung fibroblasts on collagen contraction with or without the presence of cytokines in three-dimensional culture; Effect of collagen with different concentration on the proliferation and apoptosis.RESULTS: ① Collagen gel contraction showed a dependence on the number of fibroblasts. ② Collagen gel contraction was augmented by increasing serum concentration in culture medium, and albumin increased the contraction dramatically. ③TGF and insulin significantly increased the contraction, whereas prostaglandin E2 and interleukin-1 significantly inhibited the gel contraction. ④ The lower the initial collagen concentration was, the more gel contracted and smaller final size were observed, and cell apoptosis increased.CONCLUSION: During the fibrotic process, fibroblast population migrated into the injured lung tissue may play an important role in the development of pulmonary fibrosis and serum infiltrating into injury lung tissue may play an role in stimulating the fibrotic progress. Infiltrating fluids and edema result in the dilution of the collagen concentration in the pulmonary interstitial which may lead to stronger contraction and serious fibrosis. In the dense fibrosis area, cells were hard to survive. In consequence, the final structure of fibrotic lung could not been changed and lung fibrosis progressed.
ABSTRACT
The study of the relationship between trace elements and drug resistance of tumor has been going on for a long time.It is clear that some trace elements are related to the tumor occurrence and its progress, such as selenium,zinc,copper.So they can be used as an sub index to diagnosis and to evaluate prognosis. Further study in recent years has shown that trace elements are related to the tumor drug risistance. Improveing nourishment of tumor cells may change its drug resistance and influence the curative effect of tumor. The significance of this study is to search for a simple and approach in reducing drug resistance in order to improve the chemotherapeutic effect and the patient′s prognosis.
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Purpose:To evaluate the effect of continuous intraperitoneal washing chemotherapy in treating the abdominal cavity tumor of nude mice with human ovarian epithelial cancer.Methods:The abdominal cavity tumor of nude mice models was established with human ovarian serous epithelial cancer cell line SKOV 3. 20 experimental nude mice were divided into 3 groups: the common treatment group(7 mice),the continuous washing intraperitoneal chemotherapy group(7 mice) and the control group(6 mice).All the mice were killed after two courses of treatment and the weight and volume of the cavity tumor were examined. The cell cycle expresstion rate of C erbB2 and Fas of abdominal neoplasms tissues in washing liquid were detected with FCM. Results:In the intraperitoneal washing group,the nude mice's FBW/IBW was 0.886. The volume of the cavity tumor is obviously smaller than the routine group. Significant difference in tumor growth inhibition rate was found between the routine group and the washing group.In the washing liquid, G 1 and S phase ratios were markedly lower ( P 0.05); C erbB2 rates were 66%、59% and 42% in control、common and washing group respectively, which was significant different between all groups ( P